SV40 MiR-S1 and Cellular MiR-1266 Sequester Each Other from Their Targets, Enhancing Telomerase Activity and Viral Replication

Overview

Journal Noncoding RNA

Date 2022 Aug 25

PMID 36005825

Authors

Tetsuyuki Takahashi

Hirona Ichikawa

Yukiko Okayama

Manami Seki

Takao Hijikata

Affiliations

Soon will be listed here.

Abstract

Virus-encoded microRNAs (miRNAs) target viral and host mRNAs to repress protein production from viral and host genes, and regulate viral persistence, cell transformation, and evasion of the immune system. The present study demonstrated that simian virus 40 (SV40)-encoded miRNA miR-S1 targets a cellular miRNA miR-1266 to derepress their respective target proteins, namely, T antigens (Tags) and telomerase reverse transcriptase (TERT). An in silico search for cellular miRNAs to interact with viral miR-S1 yielded nine potential miRNAs, five of which, including miR-1266, were found to interact with miR-S1 in dual-luciferase tests employing reporter plasmids containing the miRNA sequences with miR-S1. Intracellular bindings of miR-1266 to miR-S1 were also verified by the pull-down assay. These miRNAs were recruited into the Ago2-associated RNA-induced silencing complex. Intracellular coexpression of miR-S1 with miR-1266 abrogated the downregulation of TERT and decrease in telomerase activity induced by miR-1266. These effects of miR-S1 were also observed in miR-1266-expressing A549 cells infected with SV40. Moreover, the infected cells contained more Tag, replicated more viral DNA, and released more viral particles than control A549 cells infected with SV40, indicating that miR-S1-induced Tag downregulation was antagonized by miR-1266. Collectively, the present results revealed an interplay of viral and cellular miRNAs to sequester each other from their respective targets. This is a novel mechanism for viruses to manipulate the expression of viral and cellular proteins, contributing to not only viral lytic and latent replication but also cell transformation observed in viral infectious diseases including oncogenesis.

Citing Articles

Serum/glucose starvation enhances binding of miR-4745-5p and miR-6798-5p to mRNA 3'UTR: A novel method to identify miRNAs binding to mRNA 3'UTR using λN peptide-boxB sequence.

Takahashi T, Funamura M, Wakai S, Hijikata T Noncoding RNA Res. 2025; 11:188-199.

PMID: 39896348 PMC: 11786793. DOI: 10.1016/j.ncrna.2025.01.001.

References

Kenney S, Mertz J . Regulation of the latent-lytic switch in Epstein-Barr virus. Semin Cancer Biol. 2014; 26:60-8. PMC: 4048781. DOI: 10.1016/j.semcancer.2014.01.002. View

Li H, Zhao L, Funder J, Liu J . Protein phosphatase 2A inhibits nuclear telomerase activity in human breast cancer cells. J Biol Chem. 1997; 272(27):16729-32. DOI: 10.1074/jbc.272.27.16729. View

Zhao L, Yu H, Yi S, Peng X, Su P, Xiao Z . The tumor suppressor miR-138-5p targets PD-L1 in colorectal cancer. Oncotarget. 2016; 7(29):45370-45384. PMC: 5216728. DOI: 10.18632/oncotarget.9659. View

Gottwein E, Corcoran D, Mukherjee N, Skalsky R, Hafner M, Nusbaum J . Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines. Cell Host Microbe. 2011; 10(5):515-26. PMC: 3222872. DOI: 10.1016/j.chom.2011.09.012. View

Kim S, Seo D, Kim D, Hong Y, Chang H, Baek D . Temporal Landscape of MicroRNA-Mediated Host-Virus Crosstalk during Productive Human Cytomegalovirus Infection. Cell Host Microbe. 2015; 17(6):838-51. DOI: 10.1016/j.chom.2015.05.014. View

Zhang D, Liu X, Zhang Q, Chen X . miR-138-5p inhibits the malignant progression of prostate cancer by targeting FOXC1. Cancer Cell Int. 2020; 20:297. PMC: 7350594. DOI: 10.1186/s12935-020-01386-6. View

Wang X, Zhao Y, Cao W, Wang C, Sun B, Chen J . miR-138-5p acts as a tumor suppressor by targeting hTERT in human colorectal cancer. Int J Clin Exp Pathol. 2020; 10(12):11516-11525. PMC: 6966048. View

Tycowski K, Guo Y, Lee N, Moss W, Vallery T, Xie M . Viral noncoding RNAs: more surprises. Genes Dev. 2015; 29(6):567-84. PMC: 4378190. DOI: 10.1101/gad.259077.115. View

Yang S, Lickteig R, Estes R, Rundell K, Walter G, Mumby M . Control of protein phosphatase 2A by simian virus 40 small-t antigen. Mol Cell Biol. 1991; 11(4):1988-95. PMC: 359884. DOI: 10.1128/mcb.11.4.1988-1995.1991. View

10.

Sullivan C, Pipas J . T antigens of simian virus 40: molecular chaperones for viral replication and tumorigenesis. Microbiol Mol Biol Rev. 2002; 66(2):179-202. PMC: 120785. DOI: 10.1128/MMBR.66.2.179-202.2002. View

11.

Marquitz A, Mathur A, Shair K, Raab-Traub N . Infection of Epstein-Barr virus in a gastric carcinoma cell line induces anchorage independence and global changes in gene expression. Proc Natl Acad Sci U S A. 2012; 109(24):9593-8. PMC: 3386136. DOI: 10.1073/pnas.1202910109. View

12.

Vojtechova Z, Tachezy R . The Role of miRNAs in Virus-Mediated Oncogenesis. Int J Mol Sci. 2018; 19(4). PMC: 5979478. DOI: 10.3390/ijms19041217. View

13.

Broekema N, Imperiale M . miRNA regulation of BK polyomavirus replication during early infection. Proc Natl Acad Sci U S A. 2013; 110(20):8200-5. PMC: 3657827. DOI: 10.1073/pnas.1301907110. View

14.

Murphy E, Vanicek J, Robins H, Shenk T, Levine A . Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs: implications for latency. Proc Natl Acad Sci U S A. 2008; 105(14):5453-8. PMC: 2291141. DOI: 10.1073/pnas.0711910105. View

15.

Ostadrahimi S, Abedi Valugerdi M, Hassan M, Haddad G, Fayaz S, ParvizHamidi M . miR-1266-5p and miR-185-5p Promote Cell Apoptosis in Human Prostate Cancer Cell Lines. Asian Pac J Cancer Prev. 2018; 19(8):2305-2311. PMC: 6171381. DOI: 10.22034/APJCP.2018.19.8.2305. View

16.

Cazalla D, Yario T, Steitz J, Steitz J . Down-regulation of a host microRNA by a Herpesvirus saimiri noncoding RNA. Science. 2010; 328(5985):1563-6. PMC: 3075239. DOI: 10.1126/science.1187197. View

17.

Su Y, Xie R, Xu Q . Upregulation of miR-1266-5p serves as a prognostic biomarker of hepatocellular carcinoma and facilitates tumor cell proliferation, migration and invasion. Acta Biochim Pol. 2021; 68(2):293-300. DOI: 10.18388/abp.2020_5569. View

18.

Imperiale M . Polyomavirus miRNAs: the beginning. Curr Opin Virol. 2014; 7:29-32. PMC: 4149923. DOI: 10.1016/j.coviro.2014.03.012. View

19.

Pipas J . SV40: Cell transformation and tumorigenesis. Virology. 2008; 384(2):294-303. DOI: 10.1016/j.virol.2008.11.024. View

20.

Zhang W, Liao K, Liu D . MiR-138-5p Inhibits the Proliferation of Gastric Cancer Cells by Targeting DEK. Cancer Manag Res. 2020; 12:8137-8147. PMC: 7489953. DOI: 10.2147/CMAR.S253777. View